DESCRIPTION The aim of this proposal is to determine whether acute exposure to the organophosphorus insecticide chlorpyrifos causes oxidative stress in the developing brain, while the long-term objective is to test the hypothesis that oxidative stress is an underlying mechanism for the developmental neurotoxicity of organophosphates. For this purpose, rat pups at postnatal days 2 or 8, will be injected subcutaneously with different doses of chlorpyrifos (a maximal tolerated dose and two fractions of this dose). Exposure will be acute and will occur twice in a 21 hr period. Animals will be observed for clinical signs of toxicity and body weights will be recorded. Four hours after the second injection animals will be sacrificed and three brain regions (cerebellum, brainstem, forebrain) will be dissected for biochemical analyses. These will include measurements of acetylcholinesterase, ornithine decarboxylase, lipid peroxidation, reactive oxygen species, glutathione, glutathione peroxidase, superoxide dismutase and catalase, using standard procedures.